Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
2000-12-14
2001-06-19
Richter, Johann (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
Reexamination Certificate
active
06248927
ABSTRACT:
FIELD OF THE INVENTION
This invention pertains to a method for stabilizing cyclobutanone compounds and to stabilized cyclobutanone compositions. More specifically, this invention pertains to the stabilization of liquid cyclobutanone compounds with a phenolic stabilizer compound and to stabilized compositions comprising a liquid cyclobutanone compound and a phenolic stabilizer compound. The stabilization of cyclobutanone compounds with a phenolic stabilizer compound eliminates or minimizes the formation of a solid material when cyclobutanone compounds are stored and/or transported under ordinary shipping conditions.
BACKGROUND OF THE INVENTION
Cyclobutanone and its derivatives are useful intermediates in the preparation of a variety of organic compounds. For example see E. Lee-Ruff,
Adv. Strain Org. Chem
, (1991), 1, 167 and Bellus et al.,
Angew Chem
., (1988), 100(6), 820. Cyclobutanone itself can be prepared by the oxidation of cyclobutanol with chromium trioxide and oxalic acid in water as described, for example, by Krumpolic and Rocek in
Organic Synthesis Collective Volume VII
, pages 114-117. The chromium trioxide/oxalic acid oxidation is relatively non-selective and produces a dilute aqueous crude cyclobutanone mixture containing many hard-to-separate impurities. Typical impurities in the crude aqueous cyclobutanone include, but are not limited to, cyclopropanemethanol, unreacted cyclobutanol, 3-butene-1-ol, 2-butene-1-ol, cyclopropane carboxaldehyde, cyclopropane carboxylic acid, ethers and mixed ethers of cyclobutanol, cyclopropanemethanol, 3-butene-1-ol, and 2-butene-1-ol; hemi-ketals and ketals of the cyclopropanemethanol, cyclobutanol, 3-butene-1-ol and 2-butene-1-ol with cyclobutanone as well as other unknown compounds with boiling points higher and lower than cyclobutanone. Many of these impurities are color bodies and which cause the cyclobutanone product to be highly colored if not removed. Cyclobutanone having a purity of at least 99% may be obtained by a purification process comprising the steps of:
(1) distilling the aforesaid crude aqueous cyclobutanone product mixture to obtain (i) a distillate comprising cyclobutanone, water, cyclopropanemethanol, cyclobutanol, 3-butene-1-ol, 2-butene-1-ol, cyclopropane carboxaldehyde, ethers and mixed ethers of cyclobutanol, cyclopropanemethanol, 3-butene-1-ol, and 2-butene-1-ol, and hemi-ketals and ketals of cyclopropanemethanol, cyclobutanol, 3-butene-1-ol and 2-butene-1-ol with cyclobutanone; and (ii) a distillation residue comprising water, metal salts, and high boiling organic compounds such as -butyrolactone, cyclopropane carboxylic acid, and hemi-ketals and ketals of cyclopropanemethanol, cyclobutanol, 3-butene-1-ol and 2-butene-1-ol with cyclobutanone;
(2) allowing the resultant mixture to separate into (i) an organic phase comprising a minor amount of the cyclobutanone contained in the distillate and a major amount of impurities less soluble in water than cyclobutanone such as ethers, ketals, and color bodies; and (ii) an aqueous phase comprising water, a major amount of the cyclobutanone contained in the distillate, a minor amount of more hydrophilic impurities such as alcohols and cyclopropane carboxaldehyde;
(3) distilling the aqueous phase from step (2) to obtain (i) a minor amount of distillate comprising low-boiling azeotropes comprising water and organic impurities in the aqueous phase, (ii) a major amount of distillate comprising an azeotrope of water and cyclobutanone, and (iii) a distillation residue comprising water, cyclopropanecarboxylic acid, &ggr;-butyrolactone, cyclobutanol, cyclopropanemethanol, mixed ethers of the alcohols, and ketals formed from reactions between ethers and alcohols;
(4) allowing distillate (ii) from step (3) to separate into (i) a cyclobutanonerich organic phase comprising cyclobutanone, water, and one or more aldehydes having boiling points close to that of cyclobutanone and (ii) an aqueous phase comprising cyclobutanone and water; and
(5) distilling organic phase (i) from step (4) to obtain (i) a first distillate comprising an azeotrope of water and cyclobutanone, (ii) a second distillate comprising cyclobutanone having a purity of at least 90%, and (iii) a distillation residue comprising cyclobutanol, cyclopropanemethanol, mixed ethers of the alcohols, and ketals formed from reactions between ethers and alcohols.
The cyclobutanone product may contain an unacceptably high level of aldehydes, e.g., cyclopropane carboxaldehyde and cis/trans-croton-aldehyde, since such compounds are particularly difficult to remove during the purification process. The 5-step purification process described above may include an aldehyde conversion step wherein the distillations of steps (3) and/or (5) are preceded with an aldehyde conversion wherein the material to be distilled in steps (3) and/or (5) is treated with a material which converts the aldehyde to another compound or compounds having boiling points higher than the otherwise difficult-to-separate aldehydes. This ancillary step causes the aldehyde(s) present to be converted to products that have higher boiling points and, therefore, are readily separated from the cyclobutanone.
Even after meticulous purification according to the procedure described above, the cyclobutanone, which initially is obtained as a clear, colorless liquid of high purity, e.g., typically >99% pure, develops a fine, easily dispersed, white precipitate upon shipping and storage. The precipitate may form over time periods ranging from as short as several days to several months, depending upon storage and shipping conditions. The precipitate renders the material unsuitable for use, particularly in uses requiring high purity such as in the preparation of pharmaceutical compounds. The mode by which this precipitate is generated is not understood at this time, but appears to be inherent to highly purified cyclobutanone. Currently, the only way to extend the shelf life of this material is to store and ship the material under refrigeration in a darkened bottle. This adds significant expense and complications in shipping and handling without any assurance of long term stability.
Although the mode of precipitate formation is not clearly understood, others have described the thermal and photochemical degradation of cyclobutanone. See, for example, E. Lee-Ruff,
Adv. Strain Org. Chem
, (1991), 1, 167. Both the thermal and photochemical processes are believed to proceed by a common route involving the cleavage of the bond between the carbonyl and methylene unit with subsequent degradation of the diradical as shown below:
A more detailed description of the thermal decomposition of cyclobutanone can be found in M. N. Das, F. Kern, F. Cern, and T. D. Doyle,
J. Amer. Chem. Soc
., (1954) 76, 6271-6274; T. H. McGee and A. Scheifler,
Journal of Physical Chemistry
, (1972) 76, pp. 963-967; and A. T. Blades,
Can. J. Chem
., (1969) 41, 615-617. Decomposition temperatures for cyclobutanone in these studies are >360° C. The decomposition can be accelerated by the presence of oxygen, as described in R. A. Back and M. H. Back,
J. Chem. Phys
., (1979) 83, 2063-2064. However, experiments carried out in the presence of oxygen were still performed at temperatures in excess of 270° C. Therefore, cyclobutanone normally would be regarded as thermally stable at normal storage and handling temperatures.
Thermal decomposition data for 2-chlorocyclobutanone have been reported by J. Metcalfe and E. K. C. Lee,
J. Amer. Chem. Soc
., (1973) 95, 4316-4320 and for 3,3-dimethyl cyclobutanone by R. A. Smith,
J. Chem. Soc
., Perkin Trans. 2, (1977) 752-753. Certain substitution, especially the presence of electron withdrawing groups, such as nitrites, esters, or keto groups in the 2-position can significantly lower the thermal stability of the substituted cyclobutanone as described by A. H. Al-Husianni, M. Muqtar, A. S. Asrof, Tetrahedron, (1991) 47, 7719-7126.
The photochemical decomposition of cyclobutanone is described by H. O. Denschlug and K. C. Lee,
J. Amer. Chem. Soc
., (1967) 89, 4795 a
Cahill Paula Sue
Floyd Thomas Richard
Zoeller Joseph Robert
Blake Michael J.
Eastman Chemical Company
Gwinnell Harry J.
Richter Johann
Witherspoon Sikarl A.
LandOfFree
Stabilized cyclobutanone compositions does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Stabilized cyclobutanone compositions, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Stabilized cyclobutanone compositions will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2482003